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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease more prevalent in people of African and Asian origin than Caucasian origin. FcgammaRIIb is an inhibitory Fc receptor with a critical role in immune regulation. Mouse data suggest that FcgammaRIIb deficiency increases susceptibility to autoimmune disease but protects against infection. We show that a SNP in human FCGR2B that abrogates receptor function is strongly associated with susceptibility to SLE in both Caucasians and Southeast Asians. The minor allele of this SNP is more common in Southeast Asians and Africans, populations from areas where malaria is endemic, than in Caucasians. We show that homozygosity for the minor allele is associated with substantial protection against severe malaria in an East African population (odds ratio = 0.56; P = 7.1 x 10(-5)). This protective effect against malaria may contribute to the higher frequency of this SNP and hence, SLE in Africans and Southeast Asians.

Original publication

DOI

10.1073/pnas.0915133107

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

27/04/2010

Volume

107

Pages

7881 - 7885

Keywords

Asian Continental Ancestry Group, Base Sequence, DNA Primers, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Homozygote, Hong Kong, Humans, Lupus Erythematosus, Systemic, Malaria, Molecular Sequence Data, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, IgG, Sequence Analysis, DNA, United Kingdom